The endothelial cells (EC) of the vascular system are regularly exposed to a range of hemodynamic forces with great impact on cellular structures and functions. A shear-stress-dependent modulation has been reported for various endothelial functions, and first attempts were made to characterize the nature of the shear-stress-sensitive receptor. Apoptosis has been induced in cultures of vascular EC upon application of various stimuli characteristic of traumatic or pathogenic events. However, no link between apoptosis and mechanical stimulation has been reported so far-neither for vascular EC nor for other types of cells. Here we show that the lack of hemodynamic forces triggers apoptosis in endothelial cells, hinting at mechanical forces as essential stimuli for the maintenance of blood vessels.